title: Anti-cancer activity of anti-GLUT1 antibody-targeted polymeric micelles co-loaded with curcumin and doxorubicin.
abstract: BACKGROUND
  Treatment of late stage cancers has proven to be a very difficult task. Targeted therapy and combinatory drug administration may be the solution.
  
  
  OBJECTIVE
  The study was performed to evaluate the therapeutic efficacy of PEG-PE micelles, co-loaded with curcumin (CUR) and doxorubicin (DOX), and targeted with anti-GLUT1 antibody (GLUT1) against HCT-116 human colorectal adenocarcinoma cells both in vitro and in vivo.
  
  
  METHODS
  HCT-116 cells were treated with non-targeted and GLUT1-targeted CUR and DOX micelles as a single agent or in combination. Cells were inoculated in female nude mice. Established tumors were treated with the micellar formulations at a dose of 4 mg/kg CUR and 0.4 mg/kg DOX every 2 d for a total of 7 injections.
  
  
  RESULTS
  CUR + DOX-loaded micelles decorated with GLUT1 had a robust killing effect even at low doses of DOX in vitro. At the doses chosen, non-targeted CUR and CUR + DOX micelles did not exhibit any significant tumor inhibition versus control. However, GLUT1-CUR and GLUT1-CUR + DOX micelles showed a significant tumor inhibition effect with an improvement in survival.
  
  
  CONCLUSIONS
  We showed a dramatic improvement in efficacy between the non-targeted and GLUT1-targeted formulations both in vitro and in vivo. Hence, we confirmed that GLUT1-CUR + DOX micelles are effective and deserve further investigation.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston, MA , USA and.
authors.forename: Abraham H
authors.initials: AH
authors.lastname: Abouzeid
authors.forename: Niravkumar R
authors.initials: NR
authors.lastname: Patel
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Rachman
authors.forename: Sean
authors.initials: S
authors.lastname: Senn
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D051272:Glucose Transporter Type 1; D008823:Micelles; D010714:Phosphatidylethanolamines; C495677:SLC2A1 protein, human; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003474:Curcumin